2484: Establishment of the Tennessee-sickle cell disease network as a mechanism for engaging a rare disease population in patient centered outcomes research

OBJECTIVES/SPECIFIC AIMS: Despite the high prevalence of individuals diagnosed with sickle cell disease (SCD) in Tennessee, comprehensive care and education for patients with SCD is not as widely available as healthcare services for individuals managing other chronic illnesses. We aimed to engage SCD stakeholders in patient-centered outcomes research (PCOR) as a mechanism for advancing care and translational research for this rare disease population. METHODS/STUDY POPULATION: Through a partnership with the Sickle Cell Foundation of Tennessee, we implemented Community Health Ambassadors to systematically engage patient partners with SCD and their caregivers, aged 18–50 from rural and urban communities throughout Tennessee, in PCOR to establish a sustainable infrastructure, focused on connecting the SCD community through a service providing community-based organization to offer (1) information on how to connect with other families; and be informed about SCD community activities, or educational offerings; (2) training in basic research principals; and (3) opportunities to contribute to PCOR, including feedback on effective and practical ways for providing input on research efforts through patient centered input, comparing urban and rural area preferences. Community ambassadors utilized health fairs, clinic days at various hospitals and community centers, and social media to spread awareness of the project, in addition to boosting the recruitment process. RESULTS/ANTICIPATED RESULTS: A statewide SCD network was developed to offer social support and increase access to education, medical care, and engagement in research activities. Findings include: recruitment of 150 patients and 35 executive committee members (local physicians, community leaders, adults with SCD and parents of children with SCD). DISCUSSION/SIGNIFICANCE OF IMPACT: Most rural and urban families affected by SCD have no systematic way to engage in, or lend their expertise to, PCOR. A statewide network of patient partners, community stakeholders, researchers, and medical professionals will ultimately increase the standard of care for patients, and provide valuable insight for SCD research. The opportunity to create the underpinnings for coordinated patient-centered education for patients with SCD and their caregivers holds promise for developing a scalable PCOR process model for replication and implementation in other states and emulate this model with other rare disease populations

Phase 2 trial of montelukast for prevention of pain in sickle cell disease.

Cysteinyl leukotrienes (CysLTs) are lipid mediators of inflammation. In patients with sickle cell disease (SCD), levels of CysLTs are increased compared with controls and associated with a higher rate of hospitalization for pain. We tested the hypothesis that administration of the CysLT receptor antagonist montelukast would improve SCD-related comorbidities, including pain, in adolescents and adults with SCD. In a phase 2 randomized trial, we administered montelukast or placebo for 8 weeks. The primary outcome measure was a >30% reduction in soluble vascular cell adhesion molecule 1 (sVCAM), a marker of vascular injury. Secondary outcome measures were reduction in daily pain, improvement in pulmonary function, and improvement in microvascular blood flow, as measured by laser Doppler velocimetry. Forty-two participants with SCD were randomized to receive montelukast or placebo for 8 weeks. We found no difference between the montelukast and placebo groups with regard to the levels of sVCAM, reported pain, pulmonary function, or microvascular blood flow. Although montelukast is an effective treatment for asthma, we did not find benefit for SCD-related outcomes. This clinical trial was registered at www.clinicaltrials.gov as #NCT01960413

Keys to academic success for under-represented minority young investigators: recommendations from the Research in Academic Pediatrics Initiative on Diversity (RAPID) National Advisory Committee.

BackgroundAlthough Latinos, African-Americans, and American Indians/Alaska Natives comprise 34% of Americans, these under-represented minorities (URMs) account for only 7% of US medical-school faculty. Even when URMs become faculty, they face many substantial challenges to success. Little has been published, however, on keys to academic success for URM young faculty investigators.MethodsThe Research in Academic Pediatrics Initiative on Diversity (RAPID) goal is to enhance the professional advancement of URM junior faculty pursuing research careers in general academic pediatrics. One important RAPID component is the annual mentoring/career-development conference, which targets URM residents, fellows, and junior faculty, and has included 62 URM participants since its 2013 inception. A conference highlight is the panel discussion on keys to academic success for URM young investigators, conducted by the RAPID National Advisory Committee, a diverse group of leading senior researchers. The article aim was to provide a guide to academic success for URM young investigators using the 2018 RAPID Conference panel discussion. A modified Delphi technique was used to provide a systematic approach to obtaining answers to six key questions using an expert panel: the single most important key to success for URM young investigators; ensuring optimal mentorship; how to respond when patients/families say, "I don't want you to see my child because you are ____"; best strategies for maximizing funding success; how to balance serving on time-consuming committees with enough time to advance research/career objectives; and the single thing you wish someone had told you which would have substantially enhanced your success early on.Results/conclusionsThis is the first published practical guide on keys to academic success for URM young investigators. Identified keys to success included having multiple mentors, writing prolifically, being tenaciously persistent, having mentors who are invested in you, dealing with families who do not want you to care for their child because of your race/ethnicity by seeking to understand the reasons and debriefing with colleagues, seeking non-traditional funding streams, balancing committee work with having enough time to advance one's research and career by using these opportunities to generate scholarly products, and asking for all needed resources when negotiating for new jobs

Association between Hospital Admissions and Healthcare Provider Communication for Individuals with Sickle Cell Disease

Objective: To test the hypothesis that caregivers’ or adult participants’ low ratings of provider communication are associated with more hospital admissions among adults and children with sickle cell disease (SCD), respectively. Secondarily, we determined whether there was an association between the caregivers’ or participants’ health literacy and rating of providers’ communication. Methods: Primary data were collected from participants through surveys between 2014 and 2016, across six sickle cell centers throughout the U.S. In this cross-sectional cohort study, 211 adults with SCD and 331 caregivers of children with SCD completed surveys evaluating provider communication using the Consumer Assessment of Healthcare Providers and Systems (CAHPS), healthcare utilization, health literacy, and other sociodemographic and behavioral variables. Analyses included descriptive statistics, bivariate analyses, and logistic regression. Results: Participants with better ratings of provider communication were less likely to be hospitalized (odds ratio (OR) = 0.54, 95% confidence interval (CI) = [0.35, 0.83]). Positive ratings of provider communication were associated with fewer readmissions for children (OR = 0.23, 95% CI = [0.09, 0.57]). Participants with better ratings of provider communication were less likely to rate their health literacy as lower (regression coefficient (B) = −0.28, 95% CI = [−0.46, −0.10]). Conclusions: Low ratings of provider communication were associated with more hospitalizations and readmissions in SCD, suggesting the need for interventions targeted at improving patient-provider communication which could decrease hospitalizations for this population

WISE/NEOWISE Observations of Comet 103P/Hartley 2

We report results based on mid-infrared photometry of comet 103P/Hartley 2 taken during 2010 May 4-13 (when the comet was at a heliocentric distance of 2.3 AU, and an observer distance of 2.0 AU) by the Wide-field Infrared Survey Explorer. Photometry of the coma at 22 μm and data from the University of Hawaii 2.2 m telescope obtained on 2010 May 22 provide constraints on the dust particle size distribution, d log n/d log m, yielding power-law slope values of alpha = –0.97 ± 0.10, steeper than that found for the inbound particle fluence during the Stardust encounter of comet 81P/Wild 2. The extracted nucleus signal at 12 μm is consistent with a body of average spherical radius of 0.6 ± 0.2 km (one standard deviation), assuming a beaming parameter of 1.2. The 4.6 μm band signal in excess of dust and nucleus reflected and thermal contributions may be attributed to carbon monoxide or carbon dioxide emission lines and provides limits and estimates of species production. Derived carbon dioxide coma production rates are 3.5(± 0.9) × 10^(24) molecules per second. Analyses of the trail signal present in the stacked image with an effective exposure time of 158.4 s yields optical-depth values near 9 × 10^(–10) at a delta mean anomaly of 0.2 deg trailing the comet nucleus, in both 12 and 22 μm bands. A minimum chi-squared analysis of the dust trail position yields a beta-parameter value of 1.0 × 10^(–4), consistent with a derived mean trail-grain diameter of 1.1/ρ cm for grains of ρ g cm^(–3) density. This leads to a total detected trail mass of at least 4 × 10^(10) ρ kg

Adapting Medical Guidelines to Be Patient-centered Using a Patient-driven Process for Individuals With Sickle Cell Disease and Their Caregivers

Background: Evidence-based guidelines for sickle cell disease (SCD) health maintenance and management have been developed for primary health care providers, but not for individuals with SCD. To improve the quality of care delivered to individuals with SCD and their caregivers, the main purposes of this study were to: (1) understand the desire for patient-centered guidelines among the SCD community; and (2) adapt guideline material to be patient-centered using community-engagement strategies involving health care providers, community -based organizations, and individuals with the disease. Methods: From May–December 2016, a volunteer sample of 107 individuals with SCD and their caregivers gave feedback at community forums (n = 64) and community listening sessions (n = 43) about technology use for health information and desire for SCD-related guidelines. A team of community research partners consisting of community stakeholders, individuals living with SCD, and providers and researchers (experts) in SCD at nine institutions adapted guidelines to be patient-centered based on the following criteria: (1) understandable, (2) actionable, and (3) useful. Results: In community forums (n = 64), almost all participants (91%) wanted direct access to the content of the guidelines. Participants wanted guidelines in more than one format including paper (73%) and mobile devices (79%). Guidelines were adapted to be patient-centered. After multiple iterations of feedback, 100% of participants said the guidelines were understandable, most (88%) said they were actionable, and everyone (100%) would use these adapted guidelines to discuss their medical care with their health care providers. Conclusions: Individuals with SCD and their caregivers want access to guidelines through multiple channels, including technology. Guidelines written for health care providers can be adapted to be patient-centered using Community-engaged research involving providers and patients. These patient-centered guidelines provide a framework for patients to discuss their medical care with their health care providers

A Versatile and Efficient Novel Approach for Mendelian Randomization Analysis with Application to Assess the Causal Effect of Fetal Hemoglobin on Anemia in Sickle Cell Anemia

Mendelian randomization (MR) is increasingly employed as a technique to assess the causation of a risk factor on an outcome using observational data. The two-stage least-squares (2SLS) procedure is commonly used to examine the causation using genetic variants as the instrument variables. The validity of 2SLS relies on a representative sample randomly selected from a study cohort or a population for genome-wide association study (GWAS), which is not always true in practice. For example, the extreme phenotype sequencing (EPS) design is widely used to investigate genetic determinants of an outcome in GWAS as it bears many advantages such as efficiency, low sequencing or genotyping cost, and large power in detecting the involvement of rare genetic variants in disease etiology. In this paper, we develop a novel, versatile, and efficient approach, namely MR analysis under Extreme or random Phenotype Sampling (MREPS), for one-sample MR analysis based on samples drawn through either the random sampling design or the nonrandom EPS design. In simulations, MREPS provides unbiased estimates for causal effects, correct type I errors for causal effect testing. Furthermore, it is robust under different study designs and has high power. These results demonstrate the superiority of MREPS over the widely used standard 2SLS approach. We applied MREPS to assess and highlight the causal effect of total fetal hemoglobin on anemia risk in patients with sickle cell anemia using two independent cohort studies. A user-friendly Shiny app web interface was implemented for professionals to easily explore the MREPS